Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis.
2019 Dec 08
Journal Article
Authors:
Maharaj, A.R.;
Wu, H.;
Zimmerman, K.O.;
Speicher, D.G.;
Sullivan, J.E.;
Watt, K.;
Al-Uzri, A.;
Payne, E.H.;
Erinjeri, J.;
Lin, S.;
Harper, B.;
Melloni, C.;
Hornik, C.P.
Secondary:
J Clin Pharmacol
PMID:
31814149
Abstract:
Differences in fentanyl pharmacokinetics (PK) between obese and nonobese adults have previously been reported; however, the impact of childhood obesity on fentanyl PK is relatively unknown. We developed a population pharmacokinetic (PopPK) model using opportunistically collected samples from a cohort of predominately obese children receiving fentanyl per the standard of care. Using a probability-based approach, we evaluated the ability of different continuous infusion strategies to provide steady-state concentrations (C ) within an analgesic concentration range (1-3 ng/mL). Fifty-three samples from 32 children were used for PopPK model development. Median (range) age and body weight of study participants were 13 years (2-19 years) and 52 kg (16-164 kg), respectively. The majority of children (94%) were obese. A 2-compartment model allometrically scaled by total body weight provided an appropriate fit to the data. Estimated typical clearance was 32.5 L/h (scaled to 70 kg). A fixed dose rate infusion of 1 µg/kg/h was associated with probabilities between 49% and 58% for achieving C within target; however, the risk of achieving C > 3 ng/mL increased with increasing body weight (15% at 16 kg vs 43% at 164 kg). A proposed model-based infusion strategy maintained consistent probabilities across the examined weight range for achieving C within (58%) and above (20%) target. Use of an allometric relationship between weight and clearance was appropriate for describing the PK of intravenous fentanyl in our cohort of predominately obese children. Our proposed model-derived continuous infusion strategy maximized the probability of achieving target C in children of varying weights.
